The present invention relates to mathematically determining isomeric proportions within a chemical composition using a Fourier Transform Raman Spectrometer (FT-Raman) to create a standard curve.
Fourier Transform Raman Spectroscopy (FT-Raman) characterizes chemical compounds by using laser light excitation, which produces elastically scattered light (Rayleigh) and in elastically scattered light (Raman). Filtering within the FT-Raman eliminates intense Rayleigh scattering, which is typically in the range of 108 times stronger than the Raman scattering. After passing the filter, a grating disperses the light onto a detector to generate a spectrum. This spectrum provides molecular bonding information about the sample. Light loses energy to molecular vibration, inducing Raman shift, of xcexdlaserxe2x88x92xcexdscattered=xcexdRaman. Frequency range of the FT-Raman ranges from about 4000 cmxe2x88x921 to about 50 cmxe2x88x921 corrected for the Raman laser frequency. Raman use has been disclosed in such patents as U.S. Pat. No. 2,527,121 to Dudenbostel, Jr., the disclosure of which is herein incorporated by reference.
Various compounds used in inhibiting gastric acid secretion are known in the art and include a class of benzimidazole-substituted compounds, one of which is omeprazole. Omeprazole is currently used as the active pharmaceutical ingredient(API) in the commercial United States formulation PRILOSEC(copyright) (manufactured by Merck and 10 Company of Raway, N.J.). In particular, U.S. Pat. No. 4,255,431 (herein referred to as the ""431 patent) proposes such benzimidazole-substituted compounds generally described by the formula (III) in the ""431 patent that allegedly encompasses omeprazole. Various methods of making these compounds are proposed in the ""431 patent. The disclosure of U.S. Pat. No. 4,255,431 is herein incorporated by reference for the purpose of preparing omeprazole, and pharmaceutical formulations thereof.
Problematic with the ""431 patent is that the omeprazole compound has been understood to contain a singular 5-OCH3 structure on the benzimidazole moiety (see Tables 1 and 2, at Ex. 23 of the ""431 patent). Standard references also identify omeprazole as exclusively containing this xe2x80x9c5-methoxyxe2x80x9d structure, including xe2x80x9cThe United States Pharmacopeia, The National Formularyxe2x80x9d,USP 24, NF 19 (Jan. 1, 2000) at page 1217; Physicians"" Desk Reference(copyright), 51 Edition 1997 at page 516; and xe2x80x9cThe Merck Indexxe2x80x9d, Twelfth Edition 1996 at page 1174 at entry 6977, the disclosures of these references are herein incorporated by reference. Correct determination of the structure of the omeprazole (API or drug product) is necessary for proper pharmaceutical use. A recognition of the omeprazole compound as having various or differing isomeric forms in the solid state has heretofore been unrealized, as well as any determination of the amounts of individual isomeric mixtures.
The present invention relates to mathematically determining isomeric proportions within a chemical composition, specifically for an omeprazole composition having a fixed ratio of the 5-methoxy and 6-methoxy isomeric chemical components. The 5-methoxy and 6-methoxy ratio is determined with FT-Raman Spectroscopy to measure, monitor and/or control proper isomeric ratio(s) within omeprazole.